Purpose of study. We have identified the protein-coding region of the estrogen first detected this structural variant in samples. We found that whereas tissue samples containing only the common form of the mRNA showed a positive correlation between the amount of estrogen receptor (ER) mRNA and ER protein, the tissue population carrying the variant form showed no such quantitative correlation. This finding suggested that the variant form of the gene may be defective. Moreover, while the concentration of ER mRNA varied substantially among tissues carrying the common form of the gene, tissues containing the variant mRNA contained lower overall ER mRNA concentrations. We therefore wish to obtain more structural and functional information about the variant ER gene and the population of individuals carrying it. Specifically, we propose to answer the following questions: A. What is the DNA sequence of the variant ER gene? Does it give rise to a functional mutation? B. If the variant gene is functionally mutated, is the homozygous state a developmentally lethal one? C. Are there identifiable functional correlates of heterozygosity, such as late onset of puberty, early onset of menopause, amenorrhea, polycystic ovaries, or other gynecologic problems? D. Do women carrying a variant gene who develop breast cancer have relatively less responsiveness to Tamoxifen therapy and/or abnormally short survival times?